An arrhythmia is an abnormal heart rhythm. One example of an arrhythmia is bradycardia wherein the heart beats at an abnormally slow rate or wherein significant pauses occur between consecutive beats. Other examples of arrhythmias include tachyarrhythmias wherein the heart beats at an abnormally fast rate. With atrial tachycardia, the atria of the heart beat abnormally fast. With ventricular tachycardia, the ventricles of the heart beat abnormally fast. Though often unpleasant for the patient, atrial tachycardia is typically not fatal. However, some tachycardia, particularly ventricular tachycardia, can trigger ventricular fibrillation wherein the heart beats chaotically resulting in little or no net flow of blood from the heart to the brain and other organs. Ventricular fibrillation, if not terminated, is fatal. Hence, it is highly desirable to monitor increases in the risk or frequency of arrhythmia, especially in “at-risk” patients, in order to avoid or prevent arrhythmias, particularly ventricular tachycardia.
Many FDA-approved prescription and over-the-counter medications have been found to affect the likelihood and frequency of arrhythmia. Among the medications that may affect the likelihood or frequency of arrhythmia are: antibiotics such as ampicillin, clarithromycin and erythromycin; antidepressants such as Nortriptyline, Doxepin, Amoxapine; antihistamines such as diphenhydramine, and terfenadine; and many others. Many of these medications are prescribed or purchased for reasons unrelated to cardiovascular health. Such, medications may be prescribed by physicians who are unaware of the patient's cardiovascular health. Some such medications may also be bought over-the-counter by a patient without knowledge of the side effects of the medication. Moreover, the arrythmogenic effects of a medication may only appear in certain patients or when administered in combination with other medications. Thus, even where a patient is under treatment for a cardiovascular condition, and possibly at risk for arrhythmia, the patient may inadvertently take medications that increase the risk of arrhythmia. Thus, it would be particularly desirable to monitor any changes in arrhythmia risk related to the administration of medications.
Unfortunately, monitoring of the possible arrythmogenic effects of medications in individual patients is typically ad hoc and relies to a great extent on self-reporting by the patient so that the cardiovascular physician is aware of all medications the patient is taking. Unfortunately, the patient may not be sufficiently aware of changes in arrhythmia risk to report changes to the physician. The patient may also have insufficient knowledge of the side-effects of the medications the patient is taking to believe that they warrant reporting to the physician. The physician may, therefore, be unaware of the need to monitor for changes in the risk of arrhythmia in a particular patient.
One mechanism by which medications may increase the risk of arrhythmia is by prolonging the QT interval. The mechanisms underlying QT prolongation include increased transmural dispersion of repolarization (TDR). TDR is caused by differences in cellular activation and action potential durations through the ventricular wall. Transmural dispersion of repolarization has been shown to be prognostic of arrhythmic risk under a variety of conditions and studies have shown that increased TDR is associated with an increased risk of ventricular tachyarrhythmias. The T-wave of the electrocardiogram (“ECG”) is largely the result of voltage gradients created during repolarization of the myocardial cells in the three regions of the transmural wall of the heart (epicardial, mid-myocardial, and endocardial). The T-wave of the ECG is a compound electrical waveform which is the sum of the electrical waveforms resulting from differences in the repolarization time course of the myocardial cells in the three regions of the ventricles. Because the T-wave is generated by repolarization of the cells in the three regions, it is a symbol of transmural dispersion of repolarization. Studies have shown that some morphological parameters of the T-wave of the ECG are sensitive metrics of TDR, including, for example: Tapex−Tend interval, Tamplitude, Tarea, Tslope, Tmorphology, and Tcomplexity (as measured by singular value decomposition). See, e.g., C. Antzelevitch, Cardiac repolarization. The long and short of it, Europace 7(s2): S3-S9 (2005); F. Akar and D. Rosenbaum, Transmural Electrophysiological Heterogeneities Underlying Arrhythmogenesis in Heart Failure, Circ. Res. 93:638-645 (2003); and M. Yamaguchi et al., T wave peak-to-end interval and QT dispersion in acquired long QT syndrome: a new index for arrythmogenicity, Circulation 110:904 (2004), all of which are incorporated herein by reference.
However, although TDR has been shown to be prognostic of risk of arrhythmia and analysis of the T-wave of the ECG has been shown to be a sensitive metric of TDR, analyzing T-waves requires long term recording of surface ECGs and off-line analysis. Furthermore, monitoring the ECG requires the use of medical equipment that must be operated by medical personnel in a medical facility such as a physician's office. As stated above, neither the patient nor physician may believe this monitoring is required in any particular case.
Many patients who are at risk for arrhythmia are treated with an implantable cardiac stimulation device such as a pacemaker or implantable defibrillator. An implantable cardiac stimulation device, such as a pacemaker, is implanted within the patient to apply electrical pacing pulses to the heart. For bradycardia, the pacemaker may typically be programmed to pace the heart at a rate of 60 to 80 pulses per minute (ppm) to thereby prevent the heart from beating too slowly and to eliminate any long pauses between heartbeats. To prevent tachyarrhythmias from occurring, the pacemaker can be programmed to overdrive pace the heart at a rate faster than the intrinsic heart rate of the patient. Pacemakers have adjustable parameters which are programmed by the physician in an attempt to provide optimal pacing therapy. However, as described above, the patient may unknowing take medications which affect the patient's risk of arrhythmia. Taking these medications may cause changes in the cardiovascular health of the patient which may warrant reprogramming of the pacemaker. Frequent office visits are required to ensure pacemakers are optimally programmed based on the possible changes in cardiovascular health or other factors. However, even with frequent office visits, the physician cannot be completely assured that the optimal programming is provided at all times between office visits. Hence the patient may not be receiving optimal pacing therapy at all times. Thus, it would be highly desirable if such an implantable cardiac stimulation device could monitor for changes in risk of arrhythmia.
In particular, it would be desirable to have a system that could continuously monitor changes in risk of arrhythmia induced by medications.
It would also be desirable to have a system that could continuously monitor changes in risk of arrhythmia associated with medications without requiring active intervention by physician or patient.
It would further be desirable to have a system that could automatically warn the patient or a physician, nurse or manufacturer if the system detects a dangerous change in the risk of arrhythmia.
It would still further be desirable to have an implantable cardiac stimulation device that could automatically adjust its cardiac rhythm management (“CRM”) parameters based on detected changes in risk of arrhythmia.
It would yet further be desirable to have a system that could correlate changes in risk of arrhythmia with the medications taken by the patient in order to modify the medication regimen to reduce the risk of arrhythmia. We should also add using this technique to guide the modification of Rx or make recommendation to the clinician. Also, the technique could be used to monitor if the adjustments made to the medications have made a corresponding beneficial change in TMD. This could be used essentially in a closed loop system. Please add the corresponding paragraph in the spec and add the appropriate claims for these.